Discovery of Macrocyclic Peptides Armed with a Mechanism‐Based Warhead: Isoform‐Selective Inhibition of Human Deacetylase SIRT2

Designed to inhibit: by using the random nonstandard peptide integrated discovery (RaPID) system, highly potent isoform-selective inhibitors can be identified from a library of nonstandard macrocyclic peptides. These inhibitors, which contain a mechanism-based warhead residue, are active against the human deacetylase SIRT2, with IC(50) values in the low nanomolar region.